The ability of the vertebrate olfactory system to regenerate after injury, its connective plasticity, the continual replacement of sensory neurons throughout the life of the animal and its unique embryonic origins raise fundamental questions about neuron cell biology. This project focuses on a group of issues which will have significant impact upon interpretation of anatomical, neurochemical and electrophysiologicall findings. The experiments study the details of developmental events in olfaction, central reconnection after injury and the early stages of tissue differentiation and growth. The experimental methods include powerful new techniques of immunocytochemical labeling, morphometric analysis at the ultrastructural level, excitability studies of single cell s from dissociated tissues, neurons grown in culture, and new tracer techniques for study of connectivity. All of the projects are directed to issues of developmental change and the relations to regeneration and connection. We hope to find the origins of olfactory nerve Schwann cells, how growing axons penetrate the basement membrane, the effects of odors, zinc intake and environmental challenges on the rates of synthesis of receptor membrane and neuron turnover, the changes in membrane ionophores during receptor neuron differentiation and maturation, the relationships between regenerative processes in olfactory receptors and in other axotomized neurons, whether the continually turning-over neurons form effective synapses or are resorbed without functional connection, and the developmental changes in organziation of the cholinergic bulb afferents. In conjunction with the animal experiments a new type of olfactometer will be built in prototype and tested. It will make clinical evaluation of olfactory acuity simple and precise. The program is a collaborative effort to understand development, plasticity of process, form, mechanism and connectivity in that part of the vertebrate nervous system in which change is most evident. The investigators are closely associated in the univeristy community and intensely interested in the cellular processes involved in olfactory signalling.